Clinical, pathological, immunological and virological features of simian varicella virus (SVV) infection in primates are virtually identical to those of varicella zoster virus (VZV) infection in humans. Further, the SVV and VZV genomes are similar in size and structure, show striking homology in their configuration and DNA sequences, and encode antigenically related polypeptides. During latency, both viruses are present in multiple ganglia along the entire neuraxis of their respective hosts, and at least one common gene is transcribed. Finally, unlike any current animal model of varicella latency, both VZV and SVV reactivate from latently infected ganglia of their natural host. These features provide a rationale for our hypothesis that the physical state of latent SVV in monkeys is not similar, if not identical, to VZV in humans. Human ganglia cannot be removed during life, whereas monkey ganglia latently infected with SVV can be readily obtained during life. Thus, we will use in situ PCR and SVV-expressing green fluorescent protein (GFP) to identify the ganglionic cell(s) that harbors latent SVV. Also, based on our accumulating knowledge of the complete nucleotide sequences of the SVV genome, we will determine, during life, the transcriptional pattern of SVV genes in latently infected monkey ganglia. Finally, we will determine if the expression of SVV gene 21 (that is transcribed during latency in monkey ganglia) is required for establishment of latency. A detailed analysis of the physical state of latent simian varicella virus will lead to experiments designed to understand and prevent human varicella reactivation, a cause of serious neurologic disease, particularly in the rapidly increasing elderly and immunocompromised populations.